AIME201603150-M151840

Appropriate Antibiotic Use for Acute Respiratory Tract Infection inAdults: Advice for High-Value Care From the American College ofPhysicians and the Centers for Disease Control and PreventionAaron M. Harris, MD, MPH; Lauri A. Hicks, DO; and Amir Qaseem, MD, PhD, MHA, for the High Value Care Task Force of theAmerican College of Physicians and for the Centers for Disease Control and Prevention*

Background: Acute respiratory tract infection (ARTI) is the mostcommon reason for antibiotic prescription in adults. Antibioticsare often inappropriately prescribed for patients with ARTI. Thisarticle presents best practices for antibiotic use in healthy adults(those without chronic lung disease or immunocompromisingconditions) presenting with ARTI.

Methods: A narrative literature review of evidence about appro-priate antibiotic use for ARTI in adults was conducted. The mostrecent clinical guidelines from professional societies were com-plemented by meta-analyses, systematic reviews, and random-ized clinical trials. To identify evidence-based articles, theCochrane Library, PubMed, MEDLINE, and EMBASE weresearched through September 2015 using the following MedicalSubject Headings terms: “acute bronchitis,” “respiratory tract in-fection,” “pharyngitis,” “rhinosinusitis,” and “the common cold.”

High-Value Care Advice 1: Clinicians should not perform test-ing or initiate antibiotic therapy in patients with bronchitis unlesspneumonia is suspected.

High-Value Care Advice 2: Clinicians should test patients withsymptoms suggestive of group A streptococcal pharyngitis (for

example, persistent fevers, anterior cervical adenitis, andtonsillopharyngeal exudates or other appropriate combination ofsymptoms) by rapid antigen detection test and/or culture forgroup A Streptococcus. Clinicians should treat patients with anti-biotics only if they have confirmed streptococcal pharyngitis.

High-Value Care Advice 3: Clinicians should reserve antibiotictreatment for acute rhinosinusitis for patients with persistentsymptoms for more than 10 days, onset of severe symptoms orsigns of high fever (>39 °C) and purulent nasal discharge or facialpain lasting for at least 3 consecutive days, or onset of worseningsymptoms following a typical viral illness that lasted 5 days thatwas initially improving (double sickening).

High-Value Care Advice 4: Clinicians should not prescribeantibiotics for patients with the common cold.

Ann Intern Med. 2016;164:425-434. doi:10.7326/M15-1840 www.annals.org

For author affiliations, see end of text.This article was published at www.annals.org on 19 January 2016.

Acute respiratory tract infection (ARTI), which in-cludes acute uncomplicated bronchitis, pharyngi-

tis, rhinosinusitis, and the common cold, is the mostcommon reason for acute outpatient physician officevisits and antibiotic prescription in adults. Antibioticsare prescribed at more than 100 million adult ambula-tory care visits annually, and 41% of these prescriptionsare for respiratory conditions (1). Inappropriate anti-biotic use for ARTI is an important contributor to anti-biotic resistance, an urgent public health threat (2). Inthe United States, at least 2 million antibiotic-resistantillnesses and 23 000 deaths occur each year, at a costto the U.S. economy of at least $30 billion (2). Increasedcommunity use of antibiotics is highly correlated withemerging antibiotic-resistant infections. In places withgreater prescribing of broad-spectrum antibiotics, spe-cifically extended-spectrum cephalosporins and macro-lides, rates of multidrug-resistant pneumococcal dis-ease are higher (3).

Antibiotics are also responsible for the largestnumber of medication-related adverse events, impli-cated in 1 of every 5 visits to emergency departments

for adverse drug reactions (4). Adverse events range inseverity from mild (for example, diarrhea and rash) tolife-threatening (for example, Stevens–Johnson syn-drome, anaphylaxis, or sudden cardiac death). Al-though data on adverse events after inappropriate an-tibiotic use are not available, an estimated 5% to 25%of patients who use antibiotics have adverse events,and about 1 in 1000 has a serious adverse event (2).Clostridium difficile diarrhea, which can be life-threatening and is usually a result of antibiotic treat-ment, causes nearly 500 000 infections and 29 300deaths in the United States each year, leading to anestimated $1 billion in extra medical costs (5).

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Summary for Patients . . . . . . . . . . . . . . . . . . . . . . . I-34

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* This paper, written by Aaron M. Harris, MD, MPH; Lauri A. Hicks, DO; and Amir Qaseem, MD, PhD, MHA, was developed for the High Value Care Task Forceof the American College of Physicians and for the Centers for Disease Control and Prevention. Individuals who served on the High Value Care Task Force frominitiation of the project until its approval were Amir Qaseem, MD, PhD, MHA (Chair); John Biebelhausen, MD, MBA; Sanjay Desai, MD; Lawrence Feinberg, MD;Carrie A. Horwitch, MD, MPH; Linda L. Humphrey, MD, MPH; Robert M. McLean, MD; Tanveer P. Mir, MD; Darilyn V. Moyer, MD; Kelley M. Skeff, MD, PhD;Thomas G. Tape, MD; and Jeffrey Wiese, MD. Approved by the ACP Board of Regents on 19 October 2015.

CLINICAL GUIDELINE

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In 2009, direct antibiotic prescription costs totaled$10.7 billion; 62% of these costs ($6.5 billion) were at-tributed to antibiotic prescribing in the community set-ting, followed by $3.6 billion in hospitals and $527 mil-lion in nursing homes and long-term care facilities (6).An estimated 50% of antibiotic prescriptions may beunnecessary or inappropriate in the outpatient setting(7) (Unpublished data. Centers for Disease Control andPrevention), which equates to more than $3 billion inexcess costs. Over the past decade, antibiotic prescrip-tions have decreased by 18% among persons aged 5years or older in the United States; however, prescrip-tions for broad-spectrum antibiotics (fluoroquinolonesand macrolides) have increased by at least 4-fold (8).Reducing inappropriate antibiotic prescribing in theambulatory setting is a public health priority.

This article by the American College of Physicians(ACP) and the Centers for Disease Control and Preven-tion presents available evidence on the appropriateprescribing of antibiotics for adult patients with ARTI.The high-value care advice is intended to amplify ratherthan replace messages from recent clinical guidelineson appropriate antibiotic prescribing (9–19) and servesas an update of the 2001 Principles of Appropriate An-tibiotic Use for Treatment of Acute Respiratory Tract In-fections in Adults (9) and a complement to the pediatricprinciples published in 2013 (20). The target audiencefor this article is all clinicians providing care to adultsseeking ambulatory care for ARTI.

METHODSWe conducted a narrative review of evidence

about appropriate antibiotic use for treatment of pa-tients with ARTI syndromes, including acute uncompli-cated bronchitis, pharyngitis, rhinosinusitis, and thecommon cold. We included current clinical guidelinesfrom leading professional societies, such as the Infec-tious Diseases Society of America (IDSA). Clinicalguideline recommendations were augmented withevidence-based meta-analyses, systematic reviews, andrandomized clinical trials. To identify these evidence-based articles, we conducted literature searches in theCochrane Library, PubMed, MEDLINE, and EMBASEthrough September 2015. We included only English-language articles and used the following Medical Sub-ject Headings terms: “acute bronchitis,” “respiratorytract infection,” “pharyngitis,” “rhinosinusitis,” and “thecommon cold”. The focus of the article was limited tohealthy adults without chronic lung disease (such ascystic fibrosis, bronchiectasis, and chronic obstructivepulmonary disease) or immunocompromising condi-tions (congenital or acquired immunodeficiencies, HIVinfection, chronic renal failure, nephrotic syndrome,leukemia, lymphoma, Hodgkin disease, generalizedcancer, multiple myeloma, iatrogenic immunosuppres-sion, or a history of solid organ transplantation). Wepresent our findings for 4 ARTI syndromes and presenta framework for antibiotic prescribing strategies foreach (Table).

This article was reviewed and approved by theCenters for Disease Control and Prevention and by theACP High Value Care Task Force, whose members arephysicians trained in internal medicine and its subspe-cialties and which includes experts in evidence synthe-sis. The Task Force developed the high-value care ad-vice statements, which are summarized in the Figure,based on the narrative review of the literature. At eachconference call, all members of the High Value CareTask Force declared all financial and nonfinancialinterests.

ACUTE UNCOMPLICATED BRONCHITISAcute uncomplicated bronchitis is defined as a self-

limited inflammation of the large airways (bronchi) witha cough lasting up to 6 weeks. The cough may or maynot be productive (24) and is often accompanied bymild constitutional symptoms. Acute bronchitis isamong the most common adult outpatient diagnoses,with about 100 million (10%) ambulatory care visits inthe United States per year (8), more than 70% of whichresult in a prescription for antibiotics (25, 26). Acutebronchitis leads to more inappropriate antibiotic pre-scribing than any other ARTI syndrome in adults (8).

Determining the Likelihood of a BacterialInfection

More than 90% of otherwise healthy patients pre-senting to their outpatient providers with an acutecough have a syndrome caused by a virus (Table) (10,21, 22). Nonviral pathogens, such as Mycoplasmapneumoniae and Chlamydophila pneumoniae, are oc-casionally identified in patients with acute bronchitis(10), and Bordetella pertussis may be considered in sit-uations where transmission in the community has beenreported. However, determining whether a patient hasa viral or nonviral cause can be difficult. The presenceof purulent sputum or a change in its color (for exam-ple, green or yellow) does not signify bacterial infec-tion; purulence is due to the presence of inflammatorycells or sloughed mucosal epithelial cells. Acute bron-chitis must be distinguished from pneumonia. Forhealthy immunocompetent adults younger than 70years, pneumonia is unlikely in the absence of all of thefollowing clinical criteria: tachycardia (heart rate >100beats/min), tachypnea (respiratory rate >24 breaths/min), fever (oral temperature >38 °C), and abnormalfindings on a chest examination (rales, egophony, ortactile fremitus) (10, 27).

Appropriate Management StrategiesThe most recent clinical guidelines for manage-

ment of acute uncomplicated bronchitis recommendedagainst routine antibiotic treatment in the absence ofpneumonia (11). A systematic review of 15 randomized,controlled trials found limited evidence to support theuse of antibiotics for acute bronchitis and a trend to-ward increased adverse events in patients treated withantibiotics (28). A randomized, placebo-controlled trial(not included in the Cochrane review) comparingibuprofen, amoxicillin–clavulanic acid, and placebo

CLINICAL GUIDELINE Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults

426 Annals of Internal Medicine • Vol. 164 No. 6 • 15 March 2016 www.annals.org


Table. Antibiotic Prescribing Strategies for Adult Patients With Acute Respiratory Tract Infection

Variable Acute Bronchitis Pharyngitis Acute Rhinosinusitis Common Cold

Case definition Productive ornonproductive coughthat lasts up to 6 wk,with mildconstitutionalsymptoms

Sore throat (often worse withswallowing) with a usualduration of 1 wk, with possibleassociated constitutionalsymptoms

Nasal congestion, purulent nasaldischarge, maxillary tooth pain,facial pain or pressure, fever,fatigue, cough, hyposmia oranosmia, ear pressure or fullness,headache, and halitosis

Symptoms have a variable duration(1 to 33 d) and sometimes takelonger to resolve completely

Mild upper respiratoryviral illness withsneezing, rhinorrhea,sore throat, cough,low-grade fever,headache, and malaisethat lasts up to 14 d

Causes Most cases are causedby viruses: influenza,rhinovirus,adenovirus, humanmetapneumovirus,coronavirus,parainfluenza, andrespiratory syncytialvirus.

Nonviral causes includeMycoplasmapneumoniae andChlamydophilapneumoniae.

Most cases are caused by viruses.Nonviral causes occur in <15% of

cases and include group A�-hemolytic streptococci (mostcommonly) and groups C and Gstreptococci.

Rare causes includeArcanobacterium haemolyticum,Fusobacterium necrophorum,Neisseria gonorrhoeae,Corynebacterium diphtheriae,Staphylococcus aureus,Francisella tularensis,Yersinia pestis,Yersinia enterocolitica, andTreponema pallidum.

Most cases are caused by viruses,allergies, or irritants.

Nonviral causes occur in<2% of cases and includeStreptococcus pneumoniae,Haemophilus influenzae,Streptococcus pyogenes,Moraxella catarrhalis, andanaerobic bacteria.

All causes are viral.Leading causes include

rhinovirus (up to 50%);coronavirus (10% to15%); influenza (5% to15%); respiratorysyncytial virus (5%);parainfluenza (5%);and, less commonly,adenovirus,enterovirus, humanmetapneumovirus, andprobably otherunknown viruses (20).

Benefits of usingantibiotics

No benefit If the patient has a streptococcalinfection, antibiotics mayshorten the duration of illnessand prevent acute rheumaticfever or suppurativecomplications.

Limited benefit No benefit

Harms of usingantibiotics

Mild reactions: diarrheaand rash

Severe reactions:Stevens–Johnsonsyndrome

Severe infection:Clostridiumdifficile–associateddiarrhea

Life-threateningreactions:anaphylactic shockand sudden cardiacdeath

Mild reactions: diarrhea and rashSevere reactions:

Stevens–Johnson syndromeSevere infection: Clostridium

difficile–associated diarrheaLife-threatening reactions:

anaphylactic shock and suddencardiac death

Mild reactions: diarrhea and rashSevere reactions: Stevens–Johnson

syndromeSevere infection: Clostridium

difficile–associated diarrheaLife-threatening reactions:

anaphylactic shock and suddencardiac death

Mild reactions: diarrheaand rash

Severe reactions:Stevens–Johnsonsyndrome

Severe infection:Clostridiumdifficile–associateddiarrhea

Life-threateningreactions: anaphylacticshock and suddencardiac death

Antibiotic prescribingstrategy

In the absence ofpneumonia,antibiotics are notindicated.

Routine testing fornonviral causes is notrecommended.

Prescribe antipyretics andanalgesics.

�-Lactam antibiotics are indicatedwith positive results on astreptococcal test.

Antibiotics may be prescribed ifsymptoms last >10 d, severesymptoms last for >3 consecutivedays, or worsening symptoms lastafter 3 consecutive days.

Antibiotics should not beused.

Recommendedantibioticregimen

Persons withoutpenicillin allergy

Never indicated 1) Oral penicillin V, 250 mg 4times daily or 500 mg twicedaily for 10 d

2) Oral amoxicillin, 50 mg/kg ofbody weight (maximum, 1000mg) once daily or 25 mg/kg(maximum, 500 mg) twice dailyfor 10 d

3) Intramuscular benzathinepenicillin G, single dose of1 200 000 U

1) Oral amoxicillin, 500 mg, andclavulanate, 125 mg, 3 times dailyfor 5 to 7 d

2) Oral amoxicillin, 875 mg, andclavulanate, 125 mg, twice dailyfor 5 to 7 d

3) Oral amoxicillin, 500 mg 3 timesdaily for 5 to 7 d

Never indicated

Continued on following page

Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults CLINICAL GUIDELINE



showed no significant differences in the number ofdays to cough resolution (24). Although macrolides(azithromycin) are frequently prescribed for patientswith a cough, one study showed that patients withacute bronchitis treated with a macrolide had signifi-cantly more adverse events than those receiving pla-cebo (29).

Patients may benefit from symptomatic relief withcough suppressants (dextromethorphan or codeine),expectorants (guaifenesin), first-generation antihista-mines (diphenhydramine), decongestants (phenyleph-rine), and �-agonists (albuterol), although data to sup-port specific therapies are limited. �-Agonists have notbeen shown to benefit patients without asthma orchronic obstructive lung disease (30), and symptomatictherapy has not been shown to shorten the duration ofillness (30, 31). Over-the-counter symptomatic reliefhas a low incidence of minor adverse effects, includingnausea, vomiting, headache, and drowsiness (32). Pro-viders and patients must weigh the benefits and poten-tial for adverse effects when considering symptomatictherapy.

High-Value Care Advice 1Clinicians should not perform testing or initiate

antibiotic therapy in patients with bronchitis unlesspneumonia is suspected.

PHARYNGITISPharyngitis is usually a benign, self-limited illness

characterized by a sore throat that is worse with swal-lowing, with or without associated constitutional symp-toms. It is a common outpatient condition, with about12 million visits representing 1% to 2% of all ambula-tory care visits in the United States annually (33). Al-though antibiotics are usually unnecessary, they areprescribed at most visits for pharyngitis (34).


Most pharyngitis cases have a viral origin; commoncauses include rhinovirus, coronavirus, adenovirus, her-pes simplex virus, parainfluenza, enterovirus, Epstein–Barr virus, cytomegalovirus, and influenza (35). Patientswith a sore throat and associated symptoms, includingcough, nasal congestion, conjunctivitis, hoarseness, di-arrhea, or oropharyngeal lesions (ulcers or vesicles),are more likely to have a viral illness and should nothave further testing. Providers must rule out group AStreptococcus, the predominant bacterial pathogen,and exclude more serious infections (13). Patients withsymptoms suggesting a bacterial cause should betested for group A Streptococcus with a rapid antigendetection test, throat culture, or both. Suspicious symp-toms include persistent fever, rigors, night sweats, ten-der lymph nodes, tonsillopharyngeal exudates, scarla-tiniform rash, palatal petechiae, and swollen tonsils.

Clinical scoring criteria have been developed tohelp determine the likelihood of a bacterial cause. Themost widely used are the modified Centor criteria,which include fever by history, tonsillar exudates, ten-der anterior cervical adenopathy, and absence ofcough (36). Because the Centor criteria have a low pos-itive predictive value for determining the presence ofgroup A streptococcal infection, the IDSA suggests thatthey can be used to identify patients who have a lowprobability of group A streptococcal pharyngitis anddo not warrant further testing (13). Patients who meetfewer than 3 Centor criteria do not need to be tested.Those who present with unusually severe signs andsymptoms, such as difficulty swallowing, drooling, necktenderness, or swelling, should be evaluated for rarethroat infections (such as peritonsillar abscess,parapharyngeal abscess, epiglottitis, or Lemierre syn-drome). Recent data suggest that Fusobacteriumnecrophorum is implicated in approximately 10% to20% of endemic pharyngitis cases in adolescents (37,

Table—Continued

Variable Acute Bronchitis Pharyngitis Acute Rhinosinusitis Common Cold

Persons withpenicillin allergy

Never indicated – – Never indicated

No history of type Ihypersensitivity(anaphylaxis)

– 1) Oral cephalexin, 20 mg/kgtwice daily (maximum,500 mg/dose) for 10 d

2) Oral cefadroxil, 30 mg/kg oncedaily (maximum, 1 g) for 10 d

1) Oral doxycycline, 100 mg twicedaily or 200 mg once daily for 5to 7 d

2) Oral levofloxacin, 500 mg oncedaily for 5 to 7 d

3) Oral moxifloxacin, 400 mg oncedaily for 5 to 7 d

–

History ofanaphylaxis

– 1) Oral clindamycin, 7 mg/kg3 times daily (maximum,300 mg/dose) for 10 d

2) Oral azithromycin, 12 mg/kgonce daily (maximum, 500 mg)for 5 d

3) Oral clarithromycin, 7.5 mg/kgtwice daily (maximum, 250mg/dose) for 10 d

1) Oral doxycycline, 100 mg twicedaily or 200 mg once daily for 5to 7 d

2) Oral levofloxacin, 500 mg oncedaily for 5 to 7 d

3) Oral moxifloxacin, 400 mg oncedaily for 5 to 7 d

–

References 10, 11, 21, 22 12, 13 14–18 9, 19, 23




38). It has also been implicated as a cause of Lemierresyndrome (39), which is a rare and life-threatening con-dition. The role of F necrophorum in pharyngitis andsubsequent development of Lemierre syndrome war-rant further study. Routine testing for F necrophorum isnot recommended, but clinicians should remain vigi-lant and suspect Lemierre syndrome in adolescent andyoung adult patients with severe pharyngitis. Urgent di-agnosis and treatment of Lemierre syndrome is neces-sary to preclude complications and death. Other rarebacterial causes are listed in the Table. No rapid diag-nostic tests for other bacterial causes of pharyngitis ex-ist, and the risks and benefits associated with antibiotictreatment are unclear.

Appropriate Management StrategiesThe 2012 IDSA clinical guidelines recommend an-

tibiotic therapy only for patients with a positive strepto-coccal test result (13). Patients with confirmed acutegroup A streptococcal pharyngitis should be treatedfor a duration likely to eradicate group A Streptococcusfrom the pharynx (usually 10 days) with an appropriatenarrow-spectrum antibiotic. Specific regimens arelisted in the Table.

Even though most pharyngitis cases are caused byviruses, more than 60% of adults presenting with a sorethroat receive an antibiotic prescription (34). For pa-tients diagnosed with group A streptococcal infection,

Figure. Summary of the American College of Physicians and Centers for Disease and Control and Prevention advice forhigh-value care on appropriate antibiotic use for acute respiratory tract infection in adults.

SUMMARY OF THE AMERICAN COLLEGE OF PHYSICIANS AND CENTERS FOR DISEASE CONTROL AND PREVENTION ADVICE FOR HIGH-VALUE CAREON APPROPRIATE ANTIBIOTIC USE FOR ACUTE RESPIRATORY TRACT INFECTION IN ADULTS

Disease/Condition Acute respiratory tract infection (ARTI)

Target Audience Primary care providers, emergency medicine providers

Target Patient Population Healthy adults

Intervention Reduction in antibiotic prescriptions

Evidence That Using Antibiotics in PatientsWith ARTI Does Not Improve Outcomes

Multiple randomized clinical trials have shown that antibiotics are ineffective for most ARTIs. There is no benefit for patients with the common cold or acute uncomplicated bronchitis and limited benefit for patients diagnosed with bacterial rhinosinusitis.

Harms of Using Antibiotics Annual direct costs are $6.5 billion and annual indirect costs are >$30 billion in the United States.Antibiotics are responsible for 1 of every 5 emergency department visits for drug-related complications.Complications occur in 5% to 25% of patients who use antibiotics.Antibiotic-associated diarrhea caused by Clostridium difficile is the most common serious complication, responsible for 29 300 deaths in the United States per year.

Approaches to Overcome Barriers to Evidence-Based Practice

Multidimensional approaches involving active clinician education work best to reduce antibiotic prescriptions, including physician and patient education, physician audit and feedback, delayed antibiotic prescriptions, health information technology, and financial or regulatory incentives.

Talking Points for Clinicians When Discussingthe Use of Antibiotics in Patients With ARTI

The average adult has 2 to 3 episodes of ARTI per year.Symptoms usually resolve in 1 to 2 weeks, but cough can last up to 6 weeks.Symptomatic treatment tailored to patient preferences may provide relief. Antibiotics do not cure most ARTIs or reduce time to resolution of symptoms.Antibiotics cause many serious adverse effects and should be reserved for patients with confirmed group A streptococcal pharyngitis.

High-Value Care Advice High-Value Care Advice 1: Clinicians should not perform testing or initiate antibiotic therapy in patients with bronchitis unless pneumonia is suspected.High-Value Care Advice 2: Clinicians should test patients with symptoms suggestive of group A streptococcal pharyngitis (for example, persistent fevers, anterior cervical adenitis, and tonsillopharyngeal exudates or other appropriate combination of symptoms) by rapid antigen detection test and/or culture for group A Streptococcus. Clinicians should treat patients with antibiotics only if they have confirmed streptococcal pharyngitis.High-Value Care Advice 3: Clinicians should reserve antibiotic treatment for acute rhinosinusitis for patients with persistent symptoms for more than 10 days, onset of severe symptoms or signs of high fever (>39 °C) and purulent nasal discharge or facial pain lasting for at least 3 consecutive days, or onset of worsening symptoms following a typical viral illness that lasted 5 days that was initially improving (double sickening).High-Value Care Advice 4: Clinicians should not prescribe antibiotics for patients with the common cold.




antibiotics shorten the duration of sore throat by 1 to 2days, but the benefit is modest and the numberneeded to treat to reduce symptoms is 6 after 3 days oftreatment and 21 after 1 week of treatment (40). Evi-dence suggests that antibiotics may prevent complica-tions from group A streptococcal infection, includingacute rheumatic fever (which is more common in chil-dren and adolescents than adults), peritonsillar ab-scess, and further spread of group A Streptococcus inoutbreaks (40). However, little evidence supports theprevention of acute glomerulonephritis (40). Antibioticsare not recommended for chronic group A Streptococ-cus carriers because they are unlikely to spread infec-tion to close contacts and are at little or no risk forcomplications. Tonsillectomy solely to reduce the fre-quency of group A streptococcal pharyngitis in adults isnot recommended (13).

Adult patients with sore throat should be offeredanalgesic therapy, such as aspirin, acetaminophen,nonsteroidal anti-inflammatory drugs, and throat loz-enges, which can help reduce pain. Salt water, viscouslidocaine, and other mixtures are often used in clinicalpractice for topical pain relief, but there are few dataexamining these approaches. Patients can be assuredthat the typical course of a sore throat is less than 1week and that antibiotics are usually not needed be-cause they do little to alleviate symptoms and may haveadverse effects (12, 13, 40).

High-Value Care Advice 2Clinicians should test patients with symptoms sug-

gestive of group A streptococcal pharyngitis (for exam-ple, persistent fevers, anterior cervical adenitis, andtonsillopharyngeal exudates or other appropriate com-bination of symptoms) by rapid antigen detection testand/or culture for group A Streptococcus. Cliniciansshould treat patients with antibiotics only if they haveconfirmed streptococcal pharyngitis.

ACUTE RHINOSINUSITISAcute rhinosinusitis is usually a self-limited illness

resulting from a viral infection, allergy, or irritant thatcauses inflammation of the mucosal tissue in the nasaland paranasal sinus cavity. Clinical symptoms includenasal congestion and obstruction, purulent nasal dis-charge, maxillary tooth pain, facial pain or pressure, fe-ver, fatigue, cough, hyposmia or anosmia, ear pressureor fullness, headache, and halitosis. Symptom durationranges from 1 to 33 days, with most episodes resolvingwithin a week (41). More than 4.3 million adults arediagnosed with sinusitis annually, and more than 80%of ambulatory care visits result in an antibiotic prescrip-tion, most commonly a macrolide (42). Most antibioticprescriptions for this condition are unnecessary (43).


Acute rhinosinusitis is usually caused by a viralpathogen. Acute bacterial rhinosinusitis (ABRS) is con-sidered to be a secondary infection resulting from ob-struction of the sinus ostia that leads to impaired mu-

cosal clearance as a result of a viral upper respiratorytract infection (URI). Fewer than 2% of viral URIs Al-thoughare complicated by ABRS (14). The gold stan-dard for diagnosis of bacterial sinusitis is sinus punc-ture with aspiration of purulent secretions, although it israrely performed. Common bacteria isolated from sinuspuncture are listed in the Table. Radiographic imaginghas no role in ascertaining a bacterial cause (14, 44).radiologic findings, such as mucous membrane thick-ening or sinus fluid or opacity, have a sensitivity of 90%in detecting a bacterial cause, the specificity is only61% (44). Imaging is not helpful in guiding treatmentbecause viral and bacterial causes have similar radio-logic features, and it would increase costs by at least4-fold (44).

Because ABRS lacks a simple and accurate diag-nostic test, clinical guidelines recommend using clinicalsigns and symptoms to differentiate bacterial from viralcauses (15). A bacterial cause is more likely when symp-toms persist for more than 10 days without clinical im-provement, symptoms are severe (fever >39 °C, puru-lent nasal discharge, or facial pain lasting for >3consecutive days), or symptoms worsen after an initialperiod of improvement (double sickening) for morethan 3 days. In addition, a patient with new-onset fever,headache, or increased nasal discharge after a typicalviral URI that was initially improving is suspicious for abacterial cause.

Appropriate Management StrategiesThe 2012 IDSA clinical practice guidelines recom-

mend empirical antibiotics as soon as a clinical diagno-sis of ABRS is established on the basis of clinical criteria(15). Amoxicillin–clavulanate is the preferred agent,and doxycycline or a respiratory fluoroquinolone maybe used as an alternative in patients with ABRS. TheAmerican Academy of Otolaryngology–Head and NeckSurgery emphasizes watchful waiting (without antibiotictherapy) as initial management for all patients with un-complicated ABRS, regardless of severity (16). Someprofessional societies, including the American Acad-emy of Allergy, Asthma & Immunology and the Ameri-can Academy of Family Physicians, recommend amoxi-cillin as the preferred agent (17, 18). Although the IDSArecommendation is based on concern for antibiotic re-sistance, specifically ampicillin-resistant Haemophilusinfluenzae and Moraxella catarrhalis, no direct evidencesuggests that amoxicillin–clavulanate is superior. Ad-junctive therapy, such as intranasal saline irrigation orintranasal corticosteroids, has been shown to alleviatesymptoms and potentially decrease antibiotic use (15).Patients who are seriously ill, who deteriorate clinicallydespite antibiotic therapy, or who have recurrent epi-sodes should be referred to a specialist (for example,an otolaryngologist, infectious disease specialist, or al-lergist) (15).

Acute uncomplicated rhinosinusitis is a self-limitedinfection that usually resolves without antibiotics, evenin patients with a bacterial cause. Most patients diag-nosed with acute rhinosinusitis have more adverse ef-fects than benefits from antibiotics (45). A meta-analysis




of adults with acute rhinosinusitis showed that the num-ber needed to treat was 18 for 1 patient to be curedrapidly, but the number needed to harm from adverseeffects from antibiotics was 8 (45).

Most patients with acute rhinosinusitis should bemanaged with supportive care (16); analgesics may beoffered for pain, and antipyretics may be offered forfever. Additional therapies that may provide symptom-atic relief include systemic or topical decongestants,saline nasal irrigation, mucolytics, intranasal corticoste-roids, and antihistamines tailored to the patient'ssymptoms.

High-Value Care Advice 3Clinicians should reserve antibiotic treatment for

acute rhinosinusitis for patients with persistent symp-toms for more than 10 days, onset of severe symptomsor signs of high fever (>39 °C) and purulent nasal dis-charge or facial pain lasting for at least 3 consecutivedays, or onset of worsening symptoms following a typi-cal viral illness that lasted 5 days that was initially im-proving (double sickening).

COMMON COLD (NONSPECIFIC UPPER

RESPIRATORY INFECTION)The common cold, a benign, self-limited illness, is

the most common acute illness in the United States(19). It is a mild upper respiratory viral illness that mayinclude some or all of the following symptoms: sneez-ing, rhinorrhea, sore throat, cough, low-grade fever,headache, and malaise. The symptoms are dependenton the host's inflammatory response to the particularviral infection (23). Complications of the common coldinclude acute bacterial sinusitis, asthma exacerbation,and otitis media; antibiotics play no role in preventingthese complications (19, 46). There are about 37 million(3%) ambulatory care visits each year for the commoncold, and roughly 30% result in an antibiotic prescrip-tion (47).

CausesMultiple viruses have been associated with the

common cold (Table). These viruses demonstrate sea-sonality and are spread through various routes of trans-mission: direct hand contact, contact with a contami-nated environmental surface, or airborne droplets afteran infected person sneezes or coughs (48). The mostefficient means of transmission is direct hand contact;thus, the best method to reduce spread is appropriatehandwashing.

Appropriate Management StrategiesClinical guidelines state that symptomatic therapy

is the appropriate management strategy for the com-mon cold and that antibiotics should not be prescribedbecause they are not effective and lead to significantlyincreased risk for adverse effects (9, 19, 49). Patientsseeking medical advice for the common cold should beadvised that symptoms can last up to 2 weeks andshould be advised to follow up with the clinician ifsymptoms worsen or exceed the expected time of re-

covery (9, 19, 49). They should also be apprised of therisks and benefits of symptomatic therapy and shouldbe assured that antibiotics are not needed and mayhave adverse effects.

Symptomatic therapy is recommended for man-agement of common cold symptoms. Although antihis-tamines have more adverse effects than benefits whenused alone, 1 out of 4 patients treated with combina-tion antihistamine–analgesic–decongestant productshas significant symptom relief (50). Other symptomatictreatments that may offer relief include inhaled ipratro-pium bromide, inhaled cromolyn sodium, antitussives,and analgesics. Zinc supplements have been shown toreduce the duration of common cold symptoms inhealthy persons if administered less than 24 hours aftersymptom onset; however, their potential benefitsshould be weighed against adverse reactions, such asnausea and bad taste (51, 52). No evidence supportsthe use of vitamins and herbal remedies, such as vita-min C or echinacea (53, 54).

High-Value Care Advice 4Clinicians should not prescribe antibiotics for pa-

tients with the common cold.

DOES PRACTICE FOLLOW THE EVIDENCE?Antibiotic prescribing for ARTI has decreased since

the 1990s according to the National Ambulatory Med-ical Care Survey and the National Hospital AmbulatoryMedical Care Survey, but the greatest reductions havebeen seen for ambulatory care visits for children (8, 55).This may be a result of the Centers for Disease Controland Prevention's “Get Smart: Know When AntibioticsWork” campaign and program, as well as efforts bystate and local health departments to promote appro-priate antibiotic use, especially among parents andproviders who care for children (56–58). Furthermore,introduction of the pneumococcal conjugate vaccinefor children has led to decreases in pneumococcal dis-ease burden in both children and adults (59). Despiteimprovements, antibiotics are often prescribed foradults when they are not indicated, and broad-spectrum agents are prescribed at 61% of visits thatlead to an antibiotic prescription even though anarrow-spectrum agent is usually preferred (1).

HOW CAN CLINICIANS PROMOTE APPROPRIATE

ANTIBIOTIC PRESCRIPTION?Over the past 2 decades, many interventions have

been shown to decrease inappropriate antibiotic useby targeting physicians, patients, or both, includingeducation, physician audit and feedback, delayed pre-scribing strategies, financial incentives, and health in-formation technologies. Concern over patient satisfac-tion scores may limit the success of these interventionsgiven that patient pressure plays a role in antibioticoverprescribing (60). However, patient satisfaction de-pends more on the patient-centered quality of the en-counter, such as the provider spending enough time




with the patient to explain the patient's illness, than onthe receipt of an antibiotic prescription (61).

To increase patient satisfaction and decrease anti-biotic prescriptions for ARTI, we offer the followingevidence-based strategies. Clinicians can promote ap-propriate antibiotic use by labeling acute bronchitis asa “chest cold” or “viral upper respiratory infection” (62)and providing patient information sheets about appro-priate antibiotic use and alternatives to antibiotics formanaging symptoms (www.cdc.gov/getsmart) (63). Arecent study showed an 85% decrease in antibiotic pre-scribing for ARTI and increased satisfaction ratingswhen providers gave advice on symptomatic therapyand explained why antibiotics were not needed forARTI (64). A symptomatic prescription pad can be usedto provide recommendations for management ofsymptoms, allowing patients to walk away with a plan ofaction (Supplement, available at www.annals.org).When it is unclear whether an antibiotic is needed, de-layed or postdated antibiotic prescriptions (also knownas the wait-and-see approach) offer the possibility offuture antibiotic treatment if the condition does not im-prove. This approach has also been shown to increasepatient satisfaction and decrease antibiotic use (65).

Reducing antibiotic prescriptions on a largescale will require a multidimensional approach. Acommunity-level, randomized trial in Massachusettsshowed that implementing a multichannel interventionthat includes targeting physician behavior, small-groupeducation, disseminating educational materials to thecommunity, and providing provider prescribing feed-back in various settings further decreases antibioticprescription rates (66). A systematic review of 39 stud-ies showed that multifaceted interventions that com-bine physician, patient, and public education in varioussettings are most effective (67). In addition to educa-tion, examples of provider-level interventions that havebeen shown to be effective include audit and feedbackand clinical decision support (68, 69). Although it is ev-eryone's responsibility to use antibiotics appropriately,providers have the power to control prescriptions. Re-ducing inappropriate antibiotic prescribing will im-prove quality of care, decrease health care costs, andpreserve the effectiveness of antibiotics.

From the Centers for Disease Control and Prevention, Atlanta,Georgia, and the American College of Physicians, Philadel-phia, Pennsylvania.

Disclaimer: The findings and conclusions in this article arethose of the authors and do not necessarily represent theofficial position of the Centers for Disease Control andPrevention.

Acknowledgment: The authors thank Dr. Adam Hersh fromthe University of Utah for his thoughtful review and feedbackin the development of this manuscript.

Financial Support: Financial support for the development ofthis guideline comes exclusively from the operating budgetsof ACP and the Centers for Disease Control and Prevention.

Disclosures: Dr. Moyer reports that she is Chair of the Boardof Governors of the American College of Physicians. Authorsnot named here have disclosed no conflicts of interest. Disclo-sures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-1840. Any finan-cial and nonfinancial conflicts of interest of the groupmembers were declared, discussed, and resolved. A record ofdisclosures of interest is kept for each High Value Care TaskForce meeting and conference call and can be viewed at http://hvc.acponline.org/clinrec.html.

Requests for Single Reprints: Amir Qaseem, MD, PhD, MHA,American College of Physicians, 190 N. Independence MallWest, Philadelphia, PA 19106; e-mail, [email protected].

Current author addresses and author contributions are avail-able at www.annals.org.

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http://www.cdc.gov/getsmart/community/index.html

http://www.cdc.gov/getsmart/community/index.html

Current Author Addresses: Dr. Harris: Centers for DiseaseControl and Prevention, 1600 Clifton Road, Mailstop G-37,Atlanta, GA 30329.Dr. Hicks: Centers for Disease Control and Prevention, 1600Clifton Road, Mailstop A-07, Atlanta, GA 30329.Dr. Qaseem: American College of Physicians, 190 N. Indepen-dence Mall West, Philadelphia, PA 19106.

Author Contributions: Conception and design: A.M. Harris,L.A. Hicks, A. Qaseem.Analysis and interpretation of the data: A.M. Harris, L.A. Hicks,A. Qaseem.Drafting of the article: A.M. Harris, L.A. Hicks, A. Qaseem.Critical revision of the article for important intellectual con-tent: A.M. Harris, L.A. Hicks, A. Qaseem.Final approval of the article: A.M. Harris, L.A. Hicks, A.Qaseem.Statistical expertise: A. Qaseem.Obtaining of funding: A. Qaseem.Administrative, technical, or logistic support: A.M. Harris, L.A.Hicks, A. Qaseem.Collection and assembly of data: A.M. Harris.

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